The HLA (human leukocyte antigens), or so-called "histocompatibility antigens", are glycoprotein molecules found on the surface of all nucleated somatic cells, as well as all white blood cells in the human body. The HLA antigens are encoded by four loci on human chromosome six. There is a high degree of polymorphism at each locus. Initially, these antigens were used primarily in donor-recipient matching for organ transplantation. Some of these antigens have since been shown also to be associated with susceptibility to various diseases.
In particular, rheumatic disorders are believed to be closely associated with the HLA system. Notably, a number of diseases characterized by sacroilitis and with seronegative peripheral arthritis have a reported distinct association with one antigen, the HLA-B27 antigen. For individuals whose cells express B27 antigen, the relative risk for manifesting one of these diseases is 30 to 200 times that of an individual without the B27 antigen. Also, the relative risk of contracting Ankylosing Spondylitis is about 200 times greater in B27-positive than in B27-negative individuals.
Presently, the HLA system is defined by reactions of alloantisera with human leukocytes. These reactions have been interpreted as defining multiple specificities for the products of each locus. There are 47 known specificities for HLA-B antigen, one being HLA-B27. In addition, HLA antigens vary in their distribution among racial groups. Thus, an individual's race must be considered when assigning HLA phenotypes.
Generally, serologic testing for HLA antigen requires extreme caution with respect to the cross-reactivity of the antigens with the reagent sera. This is due to the fact that most antisera utilized for determining the presence of a particular antigen often cross-react with other antigens, and/or contain antibodies to other antigens.
Such is the case in serologic testing for HLA-B27, as the antisera reactive with this antigen also frequently cross-react with HLA-B7, --B22, --B40 and other antigens. Thus, at present, it is often recommended that a complete antigenic profile of all detectable HLA-A and --B antigens be performed to accurately determine expression of the HLA-B27 antigen.
Attempts have been made to replace this system with one based on monoclonal antibodies. It was believed that in view of the purity and restricted specificity of monoclonal antibodies, they would have potential for refining existing knowledge of the HLA system, as well as defining new HLA antigen relationships. Many of the monoclonal antibodies actually produced, however, recognized supertypic specificities shared by different alleles and occasionally by antigens of different loci. Thus, although several antibodies have been isolated which react with the B27 antigen, they also cross-react with numerous other B antigen alleles. Monoclonal antibodies with more restricted specificities have recently been reported, but show a concomitant loss of the ability to bind all of the known B27 variants.
Therefore, there exists a need for cell lines capable of producing a receptor, such as monoclonal antibody, specific for human HLA-B27 antigen, but which does not significantly cross-react with other HLA antigens, particularly other B locus alleles. Further, the receptor or monoclonal antibody should be capable of recognizing the polymorphic epitopic site of human HLA-B27 antigen across the various human races. The present invention fulfills this need.